Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar.

Dynamics and diversity of Escherichia coli in animals and system management of the manure on a commercial farrow-to-finish pig farm

The objective of this study was to determine the dynamics and diversity of Escherichia coli populations in animal and environmental lines of a commercial farrow-to-finish pig farm in Spain along a full production cycle (July 2008 to July 2009), with special attention to antimicrobial resistance and the presence of integrons. In the animal line, a total of 256 isolates were collected from pregnant sows (10 samples and 20 isolates), 1-week-old piglets (20 samples and 40 isolates), unweaned piglets (20 samples and 38 isolates), growers (20 samples and 40 isolates), and the finishers' floor pen (6 samples and 118 isolates); from the underfloor pits and farm slurry tank environmental lines, 100 and 119 isolates, respectively, were collected. Our results showed that E. coli populations in the pig fecal microbiota and in the farm environment are highly dynamic and show high levels of diversity. These issues have been proven through DNA-based typing data (repetitive extragenic palindromic PCR [REP-PCR]) and phenotypic typing data (antimicrobial resistance profile comprising 19 antimicrobials). Clustering of the sampling groups based on their REP-PCR typing results showed that the spatial features (the line) had a stronger weight than the temporal features (sampling week) for the clustering of E. coli populations; this weight was less significant when clustering was performed based on resistotypes. Among animals, finishers harbored an E. coli population different from those of the remaining animal populations studied, considering REP-PCR fingerprints and resistotypes. This population, the most important from a public health perspective, demonstrated the lowest levels of antimicrobial resistance and integron presence.